Aging and Altered Gravity: A Cellular Perspective

Abstract

The elderly and astronauts exhibit strikingly similar phenotypes. Although much research has addressed the comparison between these two groups at the level of the whole organism or organ level, like the musculoskeletal system, comparative studies at the cellular level remain limited. Therefore, this article aims to address this gap by conducting an extensive scoping review, comparing cell function and alterations with advanced age to those observed in altered gravity. The broad review spans different cell types and species, highlighting the generic nature of aging and its relationship to gravity. We identified 165 signs of aging at the cell level, deducted from leading aging papers, and grouped them into 11 themes: DNA and epigenetics, mitochondria, nucleus, immune system, protein and metabolism, lysosome and degradation, cell cycle, cytoskeleton, extracellular matrix (ECM), cell mechanics, and cell signaling. Following this classification, we conducted a comprehensive search using the databases Web of Science and PubMed to examine the behavior of these signs in altered gravity conditions. The results reveal that only 29% of the responses are similar in (simulated) microgravity compared to biological aging, while others show contrasting behavior, thereby highlighting the complexity of cellular responses in these conditions. However, the majority of the signs remain unexplored in altered gravity. Mechanotransduction emerges as a potential key player in the observed phenotypic resemblances between aging and microgravity. Since there still is quite a lack of knowledge of aging-related effects on a cellular level in gravity-related research, we recommend further gravity research on the many components making up the links that facilitate mechanotransduction, which can aid in understanding the origins of these shared phenotypes and could lead to new insights into age-related and space-induced health challenges.

Keywords: agingaltered gravity; hypergravity; microgravity; senescence.

FIGURE 1

A summary of comparisons between the effect of biological aging and altered gravity for the 165 identified signs of aging at a cellular level. Each theme is presented in black, followed by the items associated with that theme. The colors describe similarities and dissimilarities between the effect of altered gravity and aging by topic, while the shade indicates how many articles support this relationship.

FIGURE 2

Summary for all 165 signs of aging at the level of the cell, taken from Figure 1, showing the overall relationship between the effects of biological aging and altered gravity.

FIGURE 3

Proposed framework of the phenotype development in altered gravity compared to biological aging mechanisms. In blue: The aging mechanism as described by López‐Otín C. et al. (1) Aging starts as damage (shown in red) in primary hallmarks located mainly in the nucleus. (2) Antagonistic hallmarks act as countermeasures but will eventually become detrimental themselves, resulting in damage throughout the cell. (3) Integrative hallmarks result from the Primary and Antagonistic hallmarks and propagate damage to the cell's enviroment. In orange: Our proposed framework of the phenotype development in altered gravity. (1) Altered gravity results in poor signal translation of the mechanical environment, i.e., altered intercellular communication. (2) Antagonistic hallmarks respond to the altered intercellular communication as they act as countermeasures but will eventually become detrimental themselves. Simultaneously, this altered environment also affects the primary hallmarks. (3) Antagonistic hallmarks and, to some extent, Primary hallmarks sustain Integrative hallmarks further. We propose that unlike in biological aging, where Primary hallmarks often initiate the process, the spaceflight environment may trigger a feedback loop between Antagonistic and Integrative hallmarks, which in turn contributes to the accelerated aging phenotype. Upon returning to 1 g conditions, these effects are reversed, as the restoration of proper signal transduction terminates the cycle.